The basic premise to be tested is that a transmissible agent capable of causing autoantibody formation is present in the blood of patients with systemic lupus erythematosus (SLE). Ample evidence now exists to support a multi-factorial etiology of SLE including genetic, hormonal and environmental influences. In terms of prevention and cure, environmental influences are potentially the most susceptible to manipulation and therefore of prime importance. In previous work we had shown that the prevalence of lymphocytotoxic antibodies (LTCA) is increased in blood and nonblood relatives of SLE patients and in technicians working with lupus blood. Others have shown increased binding of denatured DNA in lupus technicians. We believe these technicians form an ideal group in which to document the presence of a transmissible agent. Their primary exposure to SLE is through the blood they handle. Unlike SLE family members they do not share the same environment with the patient, thus the likelihood of common dietary or environmental chemicals being involved is greatly reduced. These technicians will also provide an ideal group in which to assess the risk factors involved in acquisition of autoantibodies after exposure to this agent. In phase 1 of this study we will recruit a large group of technicians with different levels of exposure to SLE blood; high, medium and low. The prevalence of LCTA and ANA will be determined in technicians as well as their spouses to search for secondary transmission. Phase two will be a case control study of these individuals comparing exposure factors in autoantibody positive and negative subjects. Finally, LCTA from asymptomatic technicians will be compared to those obtained from SLE patients with respect to the effects of these antibodies on in vitro lymphocyte function to better understand the role of these autoantibodies and the pathogenesis of SLE.